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Trial record 27 of 229 for:    "essential thrombocythemia"

Exploratory Phase II Study of INC424 Patients With Primary Myelofibrosis (PMF) or Post Polycythaemia Myelofibrosis (PPV MF) or Post Essential Thrombocythaemia Myelofibrosis (PET-MF) (MACS2030)

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ClinicalTrials.gov Identifier: NCT01558739
Recruitment Status : Completed
First Posted : March 20, 2012
Results First Posted : March 3, 2015
Last Update Posted : March 3, 2015
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Primary Myelofibrosis (PMF)
Post Polycythaemia Myelofibrosis (PPV MF)
Post Essential Thrombocythaemia Myelofibrosis (PET-MF)
Intervention Drug: INC424
Enrollment 48

Recruitment Details 54 patients were screened. 48 patients were enrolled as planned.
Pre-assignment Details  
Arm/Group Title INC424
Hide Arm/Group Description Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
Period Title: Overall Study
Started 48
Completed 31
Not Completed 17
Reason Not Completed
Adverse Event             7
Withdrawal by Subject             2
Death             3
Disease Progression             4
Protocol Violation             1
Arm/Group Title INC424
Hide Arm/Group Description Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
Overall Number of Baseline Participants 48
Hide Baseline Analysis Population Description
All enrolled patients were included in the Full Analysis Set and the Safety Set.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 48 participants
69.12  (10.419)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 48 participants
Female
21
  43.8%
Male
27
  56.3%
1.Primary Outcome
Title Percentage of Participants With Treatment Success
Hide Description Treatment success was defined as a 50% or greater reduction in palpable spleen length versus baseline at 48 weeks and/or a 50% or greater improvement in total symptom score (derived from the MF symptom assessment form (MFSAF) questionnaire) versus baseline at the week 48 time point. The MFSAF assesses the following symptoms (all scored from absent (0) to worst imaginable (10)): general fatigue, abdominal pain (and discomfort), inactivity (ability to move and walk around), cough, night sweats, itching (pruritus), bone pain (diffuse not joint pain or arthritis), fever, change in appetite/unintentional weight loss (or gain) in past 6 months, overall quality of life (QoL).
Time Frame 48 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS included all participants who received at least one administration of study drug and had at least one post-baseline efficacy assessment.
Arm/Group Title INC424
Hide Arm/Group Description:
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
Overall Number of Participants Analyzed 48
Measure Type: Number
Unit of Measure: Percentage of participants
50
2.Secondary Outcome
Title Percentage of Participants With Best Overall Response
Hide Description Response to treatment and disease progression was assessed by physical examination, specifically assessing changes in spleen size by palpation. Disease response and progression was evaluated using the International Working Group for myelofibrosis Research and Treatment Response Criteria.
Time Frame week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all participants who received at least one administration of study drug and had at least one post-baseline efficacy assessment.
Arm/Group Title INC424
Hide Arm/Group Description:
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
Overall Number of Participants Analyzed 48
Measure Type: Number
Unit of Measure: Percentage of participants
Clinical improvement 6.3
Complete response 6.3
Partial response 39.6
Stable disease 47.9
3.Secondary Outcome
Title Change From Baseline in Myelofibrosis Symptoms Assessment Form (MF-SAF)
Hide Description The MF-SAF consists of seven questions about key symptoms and impact of MF. Questions are scored on a scale of 0–10, with higher scores indicating more severe symptoms and greater inactivity. Questions 1–6, which together comprise a Total Symptom Score (TSS), investigate the following symptoms: night sweats, pruritus/itching, abdominal discomfort, pain under the ribs, early satiety and bone/muscle pain. Question 7 asks patients to report levels of inactivity. The TSS reflects the sum of the scores of these symptoms excluding inactivity, with the maximum possible score being 60 (most severe symptom experienced).
Time Frame Baseline, week 4, week 12, week 24, week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Only participants from the full analysis set (FAS), who had evaluable measurements at both baseline and the post-baseline week time point, was included in the analysis for that time point. The FAS included all participants who received at least one administration of study drug and had at least one post-baseline efficacy assessment.
Arm/Group Title INC424
Hide Arm/Group Description:
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
Overall Number of Participants Analyzed 48
Mean (Standard Deviation)
Unit of Measure: score on a scale
Week 4 (n=37) -8.78  (10.638)
Week 12 (n=35) -8.46  (12.871)
Week 24 (n=30) -9.13  (11.950)
Week 48 (n=18) -7.83  (9.966)
4.Secondary Outcome
Title Change From Baseline in EQ5D Preference Index (5 Level EuroQol Questionnaire Determining Quality of Life) From Baseline
Hide Description The EQ-5D is a standardized instrument used for measuring health outcomes in a wide range of health conditions and treatment. It consists of a descriptive system and a visual analogue scale (EQ-VAS). The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The EQ-VAS records the participant's self-rated health on a vertical, VAS where the endpoints are labeled 'best imaginable health state' and 'worst imaginable health state'. The EQ-5D health state was converted to a single summary index by applying a formula that attaches a weight to each of the levels in each dimension. The final EQ5D preference index scores range from 0 to 1 with higher scores indicating better health.
Time Frame Baseline, week 4, week 12, week 24, week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Only participants from the full analysis set (FAS), who had evaluable measurements at both baseline and the post-baseline week time point, was included in the analysis for that time point. The FAS included all participants who received at least one administration of study drug and had at least one post-baseline efficacy assessment.
Arm/Group Title INC424
Hide Arm/Group Description:
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
Overall Number of Participants Analyzed 48
Mean (Standard Deviation)
Unit of Measure: unit on a scale
week 4 (n=40) 0.06  (0.173)
week 12 (n=38) 0.05  (0.178)
week 24 (n=34) 0.05  (0.231)
week 48 (n=29) 0.03  (0.222)
5.Secondary Outcome
Title Number of Hospitalizations
Hide Description Medical resource utilization (MRU) was assessed according to the number of hospitalizations.
Time Frame week 12, week 24, week 26, week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Only participants from the full analysis set (FAS), who had evaluable measurements at the post-baseline week time point, were included in the analysis for that time point. The FAS included all participants who received at least one administration of study drug and had at least one post-baseline efficacy assessment.
Arm/Group Title INC424
Hide Arm/Group Description:
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
Overall Number of Participants Analyzed 48
Mean (Standard Deviation)
Unit of Measure: number of hospitalizations
week 12 (n=48) 0.10  (0.371)
week 24 (n=40) 0.03  (0.158)
week 36 (n=37) 0.05  (0.229)
week 48 (n=35) 0.09  (0.284)
6.Secondary Outcome
Title Duration of Hospitalizations
Hide Description MRU was assessed according to the mean duration of hospitalization visits.
Time Frame week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis set, who were hospitalized between baseline and week 48, were included in the analysis.
Arm/Group Title INC424
Hide Arm/Group Description:
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
Overall Number of Participants Analyzed 9
Mean (Standard Deviation)
Unit of Measure: days
9.00  (5.852)
7.Secondary Outcome
Title Number of Accident & Emergency Visits From Baseline
Hide Description MRU was assessed according to the number of accidents and emergency room visits.
Time Frame baseline to week 12, week 12 to week 24, week 24 to week 36, week 36 to week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Only participants from the full analysis set (FAS), who had evaluable measurements at each timeframe, e.g. from baseline to week 12, were included in the analysis for that timeframe. The FAS included all participants who received at least one administration of study drug and had at least one post-baseline efficacy assessment.
Arm/Group Title INC424
Hide Arm/Group Description:
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
Overall Number of Participants Analyzed 48
Median (Full Range)
Unit of Measure: Number of visits
baseline to week 12 (n=48)
0.00
(0.0 to 2.0)
week 12 to week 24 (n=39)
0.00
(0.0 to 1.0)
week 24 to week 36 (n=33)
0.00
(0.0 to 2.0)
week 36 to week 48 (n=33)
0.00
(0.0 to 1.0)
8.Secondary Outcome
Title Number of General Practitioner (GP), Specialists' and Urgent Care Visits
Hide Description MRU was assessed according to the number of GP, specialists', and urgent care visits.
Time Frame baseline to week 12, week 12 to, week 24, week 24 to week 36, week 36 to week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Only participants from the full analysis set (FAS), who had evaluable measurements at each timeframe, e.g. from baseline to week 12, were included in the analysis for that timeframe. The FAS included all participants who received at least one administration of study drug and had at least one post-baseline efficacy assessment.
Arm/Group Title INC424
Hide Arm/Group Description:
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
Overall Number of Participants Analyzed 48
Median (Full Range)
Unit of Measure: number of visits
GP visits, baseline to week 12 (n=45)
0.0
(0.0 to 4.0)
GP visits, week 12 to week 24 (n=36)
0.0
(0.0 to 1.0)
GP visits, week 24 to week 36 (n=33)
0.0
(0.0 to 2.0)
GP visits, week 36 to week 48 (n=33)
0.0
(0.0 to 3.0)
Specialists visits, baseline to week 12 (n=47)
0.00
(0.0 to 8.0)
Specialists visits, week 12 to week 24 (n=36)
0.00
(0.0 to 2.0)
Specialists visits, week 24 to week 36 (n=33)
0.00
(0.0 to 4.0)
Specialists visits, week 36 to week 48 (n=33)
0.00
(0.0 to 3.0)
Urgent care visits, baseline to week 12 (n=48)
0.00
(0.0 to 1.0)
Urgent care visits, week 12 to week 24 (n=39)
0.00
(0.0 to 0.0)
Urgent care visits, week 24 to week 36 (n=33)
0.00
(0.0 to 1.0)
Urgent care visits, week 36 to week 48 (n=33)
0.00
(0.0 to 1.0)
9.Secondary Outcome
Title Percentage of Participants With Transfusion Dependency Status
Hide Description Transfusion dependency status from baseline through the end of study was assessed. New onset of transfusion dependency was defined as the use of 2 or more units of red blood cell products during the 8 weeks prior to a study visit. New onset of transfusion independency was defined as the use of 0 or 1 unit of red blood cell products during the 8 weeks prior to a study visit.
Time Frame baseline (BL), end of treatment (up to 28 days post last treatment) (EOT)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS included all participants who received at least one administration of study drug and had at least one post-baseline efficacy assessment.
Arm/Group Title INC424
Hide Arm/Group Description:
Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
Overall Number of Participants Analyzed 48
Measure Type: Number
Unit of Measure: Percentage of participants
From independency at BL to independency at EOT 0.0
From dependency at BL to independency at EOT 2.1
From missing at BL to independency at EOT 0.0
From independency at BL to dependency at EOT 0.0
From dependency at BL to dependency at EOT 10.4
From missing at BL to dependency at EOT 35.4
From independency at BL to missing at EOT 0.0
From dependency at BL to missing at EOT 0.0
From missing at BL to missing at EOT 52.1
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title INC424
Hide Arm/Group Description Patients diagnosed with PMF, PPV MF, or PET-MF were treated with oral INC424 at a dose of 15 - 20 mg (dose based on Baseline platelet count) twice daily.
All-Cause Mortality
INC424
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
INC424
Affected / at Risk (%)
Total   23/48 (47.92%) 
Blood and lymphatic system disorders   
Anaemia  1  3/48 (6.25%) 
Febrile neutropenia  1  1/48 (2.08%) 
Splenomegaly  1  2/48 (4.17%) 
Thrombocytopenia  1  1/48 (2.08%) 
Cardiac disorders   
Atrial fibrillation  1  1/48 (2.08%) 
Eye disorders   
Cataract  1  1/48 (2.08%) 
Eyelid ptosis  1  1/48 (2.08%) 
Gastrointestinal disorders   
Abdominal pain  1  2/48 (4.17%) 
Diarrhoea  1  1/48 (2.08%) 
Dysphagia  1  1/48 (2.08%) 
Vomiting  1  1/48 (2.08%) 
General disorders   
Hernia  1  1/48 (2.08%) 
Pyrexia  1  1/48 (2.08%) 
Infections and infestations   
Bronchopneumonia  1  1/48 (2.08%) 
Infected skin ulcer  1  1/48 (2.08%) 
Kidney infection  1  1/48 (2.08%) 
Lower respiratory tract infection  1  1/48 (2.08%) 
Progressive multifocal leukoencephalopathy  1  1/48 (2.08%) 
Staphylococcal sepsis  1  2/48 (4.17%) 
Injury, poisoning and procedural complications   
Fall  1  1/48 (2.08%) 
Musculoskeletal and connective tissue disorders   
Pain in extremity  1  1/48 (2.08%) 
Nervous system disorders   
Dizziness  1  1/48 (2.08%) 
Dysarthria  1  1/48 (2.08%) 
Migraine  1  1/48 (2.08%) 
VIIth nerve paralysis  1  1/48 (2.08%) 
Psychiatric disorders   
Disorientation  1  1/48 (2.08%) 
Renal and urinary disorders   
Renal impairment  1  1/48 (2.08%) 
Respiratory, thoracic and mediastinal disorders   
Chronic obstructive pulmonary disease  1  1/48 (2.08%) 
Cough  1  1/48 (2.08%) 
Dyspnoea  1  2/48 (4.17%) 
Epistaxis  1  1/48 (2.08%) 
Skin and subcutaneous tissue disorders   
Skin lesion  1  1/48 (2.08%) 
Surgical and medical procedures   
Cataract operation  1  1/48 (2.08%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
INC424
Affected / at Risk (%)
Total   47/48 (97.92%) 
Blood and lymphatic system disorders   
Anaemia  1  20/48 (41.67%) 
Neutropenia  1  3/48 (6.25%) 
Thrombocytopenia  1  17/48 (35.42%) 
Gastrointestinal disorders   
Abdominal distension  1  3/48 (6.25%) 
Abdominal pain  1  11/48 (22.92%) 
Abdominal pain upper  1  3/48 (6.25%) 
Constipation  1  3/48 (6.25%) 
Diarrhoea  1  11/48 (22.92%) 
Mouth ulceration  1  4/48 (8.33%) 
Nausea  1  7/48 (14.58%) 
Vomiting  1  4/48 (8.33%) 
General disorders   
Fatigue  1  11/48 (22.92%) 
Pyrexia  1  5/48 (10.42%) 
Infections and infestations   
Lower respiratory tract infection  1  7/48 (14.58%) 
Nasopharyngitis  1  3/48 (6.25%) 
Upper respiratory tract infection  1  5/48 (10.42%) 
Urinary tract infection  1  8/48 (16.67%) 
Injury, poisoning and procedural complications   
Contusion  1  11/48 (22.92%) 
Fall  1  6/48 (12.50%) 
Investigations   
Alanine aminotransferase increased  1  4/48 (8.33%) 
Platelet count decreased  1  3/48 (6.25%) 
Weight increased  1  3/48 (6.25%) 
Metabolism and nutrition disorders   
Gout  1  5/48 (10.42%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  4/48 (8.33%) 
Back pain  1  6/48 (12.50%) 
Flank pain  1  3/48 (6.25%) 
Muscle spasms  1  7/48 (14.58%) 
Pain in extremity  1  4/48 (8.33%) 
Nervous system disorders   
Dizziness  1  9/48 (18.75%) 
Headache  1  11/48 (22.92%) 
Lethargy  1  10/48 (20.83%) 
Paraesthesia  1  3/48 (6.25%) 
Psychiatric disorders   
Depression  1  3/48 (6.25%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  5/48 (10.42%) 
Dyspnoea  1  6/48 (12.50%) 
Epistaxis  1  12/48 (25.00%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  3/48 (6.25%) 
Hyperhidrosis  1  3/48 (6.25%) 
Night sweats  1  6/48 (12.50%) 
Pruritus  1  5/48 (10.42%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01558739     History of Changes
Other Study ID Numbers: CINC424AGB02
2011-005066-38 ( EudraCT Number )
First Submitted: March 16, 2012
First Posted: March 20, 2012
Results First Submitted: January 26, 2015
Results First Posted: March 3, 2015
Last Update Posted: March 3, 2015